The present invention relates generally to an apparatus or a device for treating a patient diagnosed with sleep apnea. The invention encompasses treating the patient, in one aspect, by phrenic nerve stimulation (PNS) from a device, an implanted stimulator, whose output is delivered to stimulate the patient's diaphragm to cause contraction, followed by relaxation, toward establishing a more normal breathing pattern upon detection of an episode of sleep apnea of a certain form or forms. Preferably, detection is achieved by sensing the electrical signal (EKG) generated solely by the heart without intervention of external signals applied to the heart, and to apply the sensed signals as the sole input to signal monitoring circuitry from which to determine the thoracic impedance and, therefrom, the ventilatory status of the patient.
Specific resistance of biological materials and impedance measurements have played a major role in modern medicine. The electrical conductivity and capacity of disperse systems have been described as early as 1931 (Fricke et al., The Electric Conductivity of and Capacity of Dispersed Systems; Physics 1931; 1:106-115). Later, especially in the 1950s and 1960s, significant interest was directed towards the resistance of biological materials (e.g., Geddes L. et al., The Specific Resistance of Biological Material: A Compendium of Data for the Biomedical Engineer and Physiologist, Medical and Biological Engineering 1967, 5:271-293). The application of impedance and resistance measurements for cardio-circulatory function by measuring the blood and body temperature has been studied extensively by Geddes et al., Medical and Biological Engineering 1967, 11:336-339). Also, internal and external whole body impedance measurements have been used for noninvasive monitoring and determination of cardiac output (Carter et al., Chest 2004, 125:1431-1440). In addition, the feasibility of using intracardiac impedance measurements has been evaluated by E. Alt et al. for capture detection in connection with cardiac pacing (Pace 1992, 15:1873-1879).
Background patents that describe the use of impedance in conjunction with implantable devices are referenced in U.S. Pat. No. 5,003,976 to Alt (“the '976 patent”), which describes the cardiac and pulmonary physiological analysis via intracardiac measurements with a single sensor. The '976 patent discloses that a single functional parameter, namely intracardiac impedance, varies both with the intrathoracic pressure fluctuations following respirations and with cardiac contraction. This value is representative of both pulmonary activity and cardiac activity, and can be used as well to monitor the patient's condition and cardio-circulatory status.
It is known that measurement of intracardiac impedance and associated determination of pulmonary activity is useful for detecting episodes of apnea. Many individuals suffer from apnea, which typically occurs during periods of sleep. Hence, the term “sleep apnea” has evolved, although it is possible that apnea in one or more of its forms may occur even while an individual is awake. With apnea, respiration is significantly reduced and may cease entirely for one minute or longer. In the case of sleep apnea, episodes may occur quite frequently, causing the individual to awaken from sleep as these episodes occur. In extreme cases, the individual may die from lack of oxygen (blood oxygen depletion, or hypoxia). At least three forms of sleep apnea are known.
In central sleep apnea or CSA, the condition appears to emanate from neurological causes. As frequency of the episodes of apnea increase, blood oxygen levels decrease and carbon dioxide levels increase. When the CO2 level in the blood becomes excessive, respiratory control nerve centers in the brain respond by generating signals to the phrenic nerves, which in turn, generate nerve signals to the diaphragm and chest wall muscles, causing them to expand the lungs to produce inhalation. But in patients with disturbed respiratory control in the brain, during the periods the CO2 level is increasing, the nerve signals fail to be generated with normal regularity, which means sleep can be disrupted frequently as the cycle of lowering blood oxygen level and increasing CO2 level continues until the nerves respond to awaken the patient. Or, in the worst case, until the ventilatory function fails and the individual expires.
In another form of sleep apnea, the episodes are caused by Cheyne-Stokes Respiration or CSR, an abnormal respiratory pattern characterized by alternating periods of hypopnea and hyperpnea. Hypopnea, like apnea, is a period of significantly reduced or diminished respiration, but unlike apnea, respiration continues albeit reduced, rather than ceasing entirely albeit usually only temporarily. Hyperpnea, on the other hand, is a period of fast, deep breathing. With CSR, the condition is attributable to a lag between the actual blood CO2 level and the time the respiratory control nerve centers of the brain sense that level. As a result, the respiratory control nerve centers generate signals to produce an increase in the depth and frequency of breathing in response to an apparent high blood CO2 level, when in fact the actual level has decreased. Then the brain's respiratory control nerve centers detect the drop in blood CO2 level and act to slow respiration, when in fact the actual level has increased. This causes an increasingly unbalanced cycle of respiration that alternates between hypopnea and hyperpnea, which may become so severe that breathing ceases between the periods of hyperpnea, a condition referred to frank apnea. The episodes of apnea can cause patient arousal from sleep because of blood oxygen depletion, but the arousal typically is brief (only a few seconds) and may occur numerous times during a single night. Here also, a worst case situation is possible. CSR is often (but not necessarily) associated with congestive heart failure (CHF). From time to time herein, this form of sleep apnea may be referred to as CSR, but it will be understood that the meaning of that terminology is CSR-induced apnea or apnea attributable to CSR.
A third form of sleep apnea is obstructive sleep apnea or OSA, which is caused by temporary blockage of the individual's ventilation airway. This condition is deemed to be attributable to weakness of the muscles around the soft palate, occurring most often in individuals with obesity or with increasing age, such that during sleep these muscles relax and the soft palate assumes a position that obstructs the airway. As a result of this blockage, inadequate amounts of oxygen are delivered to the lungs and the blood CO2 level increases, to a point that the response of the respiration control nerve centers of the brain act typically to awaken the individual for resumption of normal breathing until the next obstruction of the airway occurs.
Various techniques have been advanced in an effort to correct the several forms of sleep apnea. In the case of CSA, detection of an episode by an implanted device may be responded to by direct electrical stimulation of the phrenic nerves from the device via transvenously implanted leads and electrodes whereby to deliver periodic stimulation signals from the phrenic nerves to the diaphragm to cause the latter to cyclically contract and relax in resumption of normal respiratory rhythm. This type of phrenic nerve stimulation therapy or so-called diaphragmatic pacing is described, for example, in U.S. Pat. No. 5,056,519 to Vince; U.S. Pat. No. 6,415,183 to Scheiner et al.; and U.S. Pat. No. 6,641,542 to Cho et al.
If the sleep apnea is attributable to CSR, proposed treatment techniques may address alleviation of the typical source of the disorder, namely CHF, through cardiac pacing alone, as described, for example, in U.S. Pat. No. 7,706,881 to Benser. However, Benser suggests a sustained increase in cardiac output, rather than detection of and response to individual episodes, for suppressing apnea/hypopnea, and states that the increase is beneficial in and of itself by tending to mitigate CHF and pulmonary edema. Alternatively, diaphragmatic pacing attributable to phrenic nerve stimulation may be used as the therapy for suppressing or terminating the apnea induced by CSR, as described for example, in U.S. Pat. No. 7,371,220 to Koh et al (“the '220 patent”).
In the case of OSA, a conventional treatment involves nightly wearing by the patient of breathing apparatus that provides continuous positive airway pressure or bi-level positive pressure therapy. It has also been suggested that direct electrical stimulation of muscle adjacent or near the soft palate from an implanted device responsive to episodes of OSA may be suitable to produce sufficient toning of the muscle so as to remove obstruction of the airway and enable resumption of normal breathing pattern, as described, for example, in the '220 patent.
In some instances, a combination of therapies, such as cardiac pacing and diaphragmatic pacing (phrenic nerve stimulation, or PNS) may be used to achieve the desired restoration of normal or near normal breathing pattern, depending on the particular condition or types of condition suffered by the patient, as disclosed, for example, in U.S. Pat. No. 7,357,775 to Koh (“the '775 patent”). In any of these various forms of sleep apnea, it has also been suggested as desirable to generate warning signals as by vibration or tickle voltage from the implanted device or by telemetry to a bedside alarm or monitor to awaken the patient, in addition to delivery of the therapy or if the therapy is proving ineffective, during a detected episode.
In some cases, these forms of therapy are delivered continuously while the patient is asleep, without regard to whether an episode of sleep apnea is occurring. It would be desirable to detect each episode of sleep apnea as it occurs, and thereupon deliver the appropriate therapy rather than deliver continuous albeit unneeded therapy. This is an important aspect regarding the battery capacity and service life of an implanted stimulation device.
It has been found that cessation of respiration for a period of time may not be truly indicative of onset of an episode of sleep apnea. That is, it may constitute a false detection of apnea, or a false positive, when in fact the patient is otherwise experiencing proper breathing. To avoid false positives, and the consequent delivery of an unnecessary therapy, a conventional technique employed in detection of an episode of sleep apnea is to suppress delivery of therapy unless little or no respiration is detected for a period of time exceeding, for example, twenty seconds as satisfaction that an episode is indeed occurring. However, this technique has the disadvantage that it may prevent prompt detection of actual apnea, with concomitant delay in delivery of appropriate therapy.
Various techniques have been advanced in the art for detecting episodes of sleep apnea (whether or not including hypopnea), as disclosed, for example, in the '220 patent; U.S. patent application Ser. No. 10/795,009 of Koh; and the '775 patent. Once an episode of sleep apnea is detected, therapy is delivered to terminate the episode and restore more normal respiration.
A technique for detecting thoracic impedance and ventilatory status of an individual from information derived by sensing cardiac signals generated by electrical energy of the heart alone is disclosed in the aforementioned related co-pending U.S. patent application Ser. No. 12/807,706 (“the '706 patent application) of the same inventors as in the present application. The sensed cardiac signals are applied as the sole input to signal detection circuitry, from which a factor or parameter related to intrathoracic, intracardiac or thoracic impedance and ventilation function of the patient is derived, and to changes in that impedance and ventilation, as an indication of the status of a physical condition of the patient, in particular, congestive heart failure and treatment thereof.
Prior reported attempts to determine impedance measurements and/or associated ventilatory status of a patient from internal signals in the body had used external (to the heart) power sources to stimulate the heart or to provide currents through the thorax. The resulting cardiac signals or current amplitudes in the thorax were then sensed and applied to detection devices for monitoring and measuring impedance and/or associated ventilatory status. This external energy might be applied either from an implantable device using energy from its own battery or from a supply external to the body.